Harrisvaccines Awarded National Institute of Food and Agriculture Grant for Swine Disease Research

AMES, Iowa, October 1, 2013 – Ames, Iowa-based vaccine producer, Harrisvaccines, today announced it has been awarded a grant from the USDA National Institute of Food and Agriculture (NIFA) for Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) research. This project is supported by Agriculture and Food Research Initiative Grant no. 2013-67015-21307 from the USDA National Institute of Food and Agriculture.

The grant, titled Proteomics-defined Porcine Reproductive and Respiratory Syndrome Virus Immunoproteome, will be a two-year project, beginning on October 1, 2013. Dr. Mark Mogler, Head of Research for Harrisvaccines, and Dr. Kurt Kamrud collaborated in achieving the grant with Dr. Manohar John of PathoVacs. Dr. Mogler will be serving as Project Director.

The basic research project will focus on a new way of looking for protective determinants of the PRRS virus. Harrisvaccines will be generating protein fragment libraries of PRRSV strains and the PRRSV protein fragment libraries will be screened using innovative technology developed by their collaborator on the project, Dr. John.

“Dr. John has a novel technology that allows him to screen thousands of antigens at a time,” said Dr. Mogler. “This will be very beneficial, because rather than looking at only one antigen at a time, we will be able to look at tens of thousands simultaneously.”

During the first year of the project, Harrisvaccines will be generating the fragments and creating fragment libraries for screening; screening will also be done during the first year. The second year of the project will mainly consist of data analysis and confirmatory testing.

At the end of the two years, Dr. Mogler is confident that Harrisvaccines will be able to characterize the immune response to PRRSV proteins by identifying reactive sites that otherwise, would not have been found.

“Ideally we would find a sequence, or a set of sequences, that are found across all PRRSV strains. We could then use these to make a more effective PRRSV vaccine,” Dr. Mogler explained.

About Harrisvaccines

Headquartered in Ames, Iowa, Harrisvaccines focuses on revolutionizing animal health vaccines and enhancing productivity in the swine, cattle, equine, and farmed aquaculture industries. Using state-of-the-art advanced molecular science, Harrisvaccines employs their unique SirraVaxSM RNA Particle (RP) technology platform to develop rapid-response, herd-specific products for animal diseases. To learn more about Harrisvaccines, visit www.harrisvaccines.com.

About PathoVacs

PathoVacs Incorporated is an early stage Biotechnology Company based in Ames, IA. The Company is based on a highly innovative proteome mining platform for novel protein antigen discovery for development of broadly protective/universal subunit vaccines against infectious agents that cause diseases in humans, livestock and poultry.  

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Harrisvaccines Inc. Tailgate to Benefit Local Animal Shelter

Ames, Iowa (October 24, 2012)- The idea of 20,000 different homeless citizens, over the past 20 years, passing through a single shelter in a small college town would normally be seen as an unacceptable neglect of one’s basic needs, and yet that is the reality for one local Iowa shelter. The facility is none other than Ames Animal Shelter, and although the inhabitants are not of our species they still requires the same basic necessities, and then some. In light of their commitment to service and compassion towards animals in need, the locally based animal vaccine company Harrisvaccines Inc. has organized a tailgating fundraiser where all the proceeds will be donated to the Ames Animal Shelter.

The tailgate will begin at 4 p.m. in lot B6 of Jack Trice Stadium. The event will be hosted by a number of Harrisvaccines employees, and their families, and is welcoming anyone who is looking to enjoy some pregame festivities and be a part of a noble cause. The meal bundles will be available for $4 each from 4 p.m. to 6 p.m. Again, all the funds collected from this event will be going towards the shelters continued success in saving and improving lives in the Ames community.

The funds that the shelter receives will be used for the continued improvement of the staff’s and volunteers’ ability to care for and house these animals whom most have rarely, if ever, had a roof over their heads or a comfortable, safe place to sleep. These upgrades will manifest in a number of ways, including: more skills training for staff/volunteers, increased informational/educational outreach and awareness in the Ames area, more comfortable accommodations for the animals and workers alike, and any other projects as they present themselves. Through these improvements, the staff of Ames Animal Shelter hopes to be able to maintain and/or increase their 90% adoption rate, for the foreseeable future.

Harrisvaccines will continue to reach out into the Ames community, and others, for opportunities to service its citizens’ needs. As a small, local business they hope to deeply integrate themselves into the community as a sign of loyalty and commitment to the proud, local brand of Ames, Iowa.

About Harrisvaccines

Headquartered in Ames, Iowa, Harrisvaccines focuses on revolutionizing animal health vaccines and enhancing productivity in the swine, cattle, equine, and farmed shrimp industries. Using state-of-the-art advanced molecular science, Harrisvaccines employs a unique RNA platform to develop products for animal diseases. For more information, visit http://www.harrisvaccines.com.

Contact:

Anja Dekkers, Customer Service and Marketing Representative

Harrisvaccines Inc.

adekkers@harrisvaccines.com

(515)291-9904

Harrisvaccines Awarded Vaccine Product Licensure

USDA Licenses Swine Flu Vaccine, Approves Production Facility

AMES, Iowa – Harrisvaccines announces United States Department of Agriculture (USDA) licensure of the company’s swine flu vaccine, approved by the Department’s Center for Veterinary Biologics (CVB) for disease caused by swine influenza virus (SIV) H3N2.

The vaccine is the first to be licensed by the USDA CVB that utilizes RNA Particle Technology. Dr. Kurt Kamrud, Vice President of Research and Chief Scientific Officer at Harrisvaccines, led the company’s development and application of RNA Particle Technology – with the ultimate goal of producing a swine influenza vaccine that could be manufactured faster and safer than those produced using modified live or inactivated/killed virus technologies.

This groundbreaking platform allows for the manufacture of vaccines without ever isolating a live virus from infected animals.  Only a gene from an infected animal is required to prepare vaccines in as little as four weeks.

The vaccine, licensed as Swine Influenza Vaccine, RNA, Product Code 19A5.D0, was initially submitted to USDA CVB for licensing in 2009.

“When we submitted our license application in 2009, the USDA didn’t have an established category into which the product fit,” said Jodi French, USDA Liaison at Harrisvaccines.  “There were additional regulatory hoops to jump through in order to achieve this first license.”

In addition to USDA licensure of the vaccine, Harrisvaccines received a United States Veterinary Biologics Establishment License, #592, which approves the Ames-based facility for future manufacture of new vaccines for a broader spectrum of veterinary applications, from swine and cattle to companion animal and farmed aquaculture.

“We were founded in 2006, so this has been a long, challenging road to licensure for a novel technology to be used in animal health,” Harrisvaccines founder and President Dr. D.L. “Hank” Harris said. “These USDA licenses mark a major milestone, and perhaps most importantly, signal that this technology is a key fixture in our country’s continuing fight against biological threats and ever-changing pathogens.”

“With USDA licensure of both the SIV H3N2 vaccine and our Ames manufacturing facility, we expect additional licenses for vaccines manufactured using RNA Particle Technology to be issued on more condensed timelines. With new strains of this virus identified as recently as July of this year, we’re particularly interested in our potential to manufacture custom, farm-specific vaccines in a matter of weeks instead of months,” Harris said.

About Harrisvaccines

Headquartered in Ames, Iowa, Harrisvaccines focuses on improving animal health and enhancing productivity in the swine, cattle, equine and farmed shrimp industries. Harrisvaccines employs two unique RNA platforms to develop custom farm-specific vaccine products against animal diseases. For more information, visit www.harrisvaccines.com.

Alphavirus Platform: Interview with Dr. Kamrud

Dr. Kurt Kamrud, Vice President of Research and Chief Scientific Officer for Harrisvaccines, is an expert in the field of infectious diseases. After completing his doctorate in microbiology, focusing on the use of alphavirus vectors to examine insect/virus interactions, he conducted research at the United States Army Medical Research Institute for Infectious Diseases (USAMRID) developing alphavirus replicon-based vaccines. Prior to joining Harrisvaccines in 2010, Dr. Kamrud served as the Director of Discovery at AlphaVax, Inc., the commercial developer of the alphavirus replicon vaccine system used at Harrisvaccines. Dr. Kamrud has been granted four international patents pertaining to the alphavirus replicon system. Here he explains more in depth the alphavirus platform used to produce vaccines at Harrisvaccines.

Question: Could you give an overview of the alphavirus platform used at Harrisvaccines?

Answer: Alphaviruses are positive-sense, single-stranded RNA viruses found in the Togaviridae family of viruses.  They have a broad host range and therefore are capable of replicating in many vertebrate and invertebrate cells. Expression vectors have been engineered from Alphaviruses in which the structural protein gene region has been replaced by heterologous genes and have been shown to express high levels of the heterologous protein in cultured cells. These RNA vectors, known as replicons, are capable of replicating on their own but are not packaged into virus-like particles unless the structural proteins are provided in trans. Thus, replicons are single cycle vectors incapable of spreading from infected to non-infected cells.

Question: Why was this platform an area of focus?

Answer: Because of the features I just described, Alphavirus replicon vectors are being developed as a platform vaccine technology for numerous viral, bacterial, protozoan and tumour antigens where they have been shown to be efficient inducers of both humoral and T cell responses. In addition, as the Alphavirus structural proteins are not expressed in vaccine recipients, anti-vector immune responses are generally minimal, allowing for multiple effective immunizations of the same individual.

Question: What are the benefits verses traditional vaccines?

Answer: Advances in the fields of molecular biology, virology and recombinant DNA technologies have led to development of replicon-based vaccines that extend the scope of vaccination to noninfectious diseases and therapeutic vaccination; areas that traditional live attenuated or recombinant subunit approaches have struggled to excel in.

Question: How did this platform come to light and what had been done previously to address the challenge?

Answer: Development of Alphavirus expression vectors began with the study of defective interfering (DI) particles.  DI particles were used to identify the cis-acting sequences essential for replication and packaging of Alphavirus RNAs.  Key discoveries started in the late 1980’s and continued through the late 1990’s.

Question: Who was involved in this discovery?

Answer: The original discoveries came out of academic laboratories both in the United States and in Europe.  The U.S. Army also played an important role in extending the use of alphavirus replicon systems; a human vaccine company named AlphaVax refined manufacturing processes and conducted the first-ever human clinical evaluations with the system.  Subsequently, Harrisvaccines has advanced the replicon system toward USDA regulatory approval and commercial veterinary use.

Question: What was the “aha” moment?

Answer: Because Alphaviruses have a positive-sense RNA genome, full-length cDNA clones of them could be used to generate RNA transcripts that, when introduced into cells, would initiate a complete virus replication cycle and generate infectious virus.  The full-length cDNA clones then served as a DNA-based tool to study an RNA virus genome; study of DI genomes isolated from preparations of live virus then lead to the development of replicon systems in use today.

Question: What challenges have you run into during the process of taking the vaccine closer to USDA licensure?

Answer: Initial characterization of Alphaviruses and the exploitation of their genomes to develop replicon vector systems has occurred over nearly a 30 year time span.  The development of the first licensed replicon-based vaccine for use in veterinary applications will occur very soon; a process that has taken 6 years.

Hello, my name is Dr. Hank Harris, and I’m an Entrepreneur

As with any novel technology, one of the biggest obstacles is to educate the early adopters and early majority of Roger’s innovation adoption bell curve while servicing the innovators. This forum will try to add to innovators’ toolbox of information for acceptance of replicon particle (RP) vaccine technology to replace current traditional vaccine methods.

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Dr. Hank Harris

 

One of the biggest surprises to me while running Harrisvaccines, was the company’s participation in this eventual application to all production livestock management. While the mission of then Sirrah LLC was to solve the worst economically devastating virus in modern commercial swine production, the journey of a true startup company and my own self-acceptance as an entrepreneur is why Harrisvaccines is now positioned to be the world leader in for RP vaccines for veterinary purposes.

 

Harrisvaccines initially was founded as Sirrah, LLC by my wife, Dr. Isabel Turney Harris, and myself in 2005, along with my postdoctoral student at the time, Dr. Matt Erdman. It was the culmination of recent research in swine and the building of relationships with a human vaccine company, Alphavax, starting in 2002. Then, I was splitting my time between swine and shrimp research. It had only been a few years since bringing shrimp into Kildee Hall at Iowa State University, but there was still so much interest in Porcine Reproductive Respiratory Syndrome Virus (PRRSV) since being identified in the early 90’s. Upon discovering protective genes in the PRRS virus, Dr. Erdman and I filed a disclosure for a patent with ISU. As university employees you must file a disclosure then ISU owns that patent. Because of the large PRRS virus patent portfolio of other companies like Boehringer Ingelheim (BI), Erdman and I got the idea to license back our patent to spin out a company. Thus, Sirrah, LLC (Harris backwards). Looking back, I see this as a logical step only because I had done it before in the 80’s with Nobl Labs, which was eventually purchased by BI.

 

But Sirrah would have never come to be without the chance relationship building with the scientific and business team at Alphavax in the Research Triangle Park in Chapel Hill. We had genes from the PRRS virus that we showed experimental protection through live virus, but we wanted a delivery system to circumvent live virus inoculation. Erdman had done some preliminary research on Alphaviruses and found that Alphavax had tied up all the essential intellectual property. I told Matt to call them up. That phone call resulted in a now almost 10 year relationship which began proof of concept that Alphavax’s RPs would work in swine and produce an immune response. Once proven that Biosafety level 2 (BL2) RPs worked in swine, then an exclusive license to develop the technology for use in swine in three diseases; PRRSV, Swine Influenza virus (SIV), and Porcine Circovirus (PCV2).

 

After successful technology transfer and good initial sales, Iowa Farm Bureau came in as a large investor and Sirrah LLC was reincorporated as Harrisvaccines, a C-corporation.

 

Even in the two years, a tremendous amount has changed in the company. It has taken this long to educate the regulators at the Center for Veterinary Biologics to the safety and efficacy of RPs. Now we are in the home stretch of our first USDA licensed product (Swine Influenza Vaccine, RNA) and a USDA licensed facility. We have added a substantial amount of products for animal diseases to our pipeline including a potential autogenous line. Although Swine and Shrimp research has been our cash flow system, we now have our targets on protective genes for diseases in Cattle, Horses, and Poultry.

 

ISU is very supportive because it revolves around economic development in Iowa.  Plus they provide Harrisvaccines with brilliant people and facilities. Harrisvaccines is a poster child for Iowa Farm Bureau and ISU, not because of the number of employees but because of the type of people we employ. Our average employee age is under 30; several employees have PhDs, and several are working towards earning their PhDs. We also employ local people in the community without technical or scientific background. A wide variety of people.

 

I have to admit I didn’t see this in the beginning. I’m a problem solver and approach problems laterally. As an entrepreneur, I find myself trying to instill in the company all the mistakes I’ve made in this company and in companies before. Even though I’ve started a company and worked for a large successful company, I never applied business principals until Harrisvaccines. We are ready to go it alone and change the way our food chain is protected from ever-changing diseases.

Swine Dysentery Too Costly to Live With

By D. L. Hank Harris, DVM, Ph.D.,

Founder and President of Harrisvaccines 

Swine Dysentery (SD), commonly known as bloody scours, is a troublesome disease which had been virtually eliminated through scientific breakthroughs in the 1970s and 1980s.

But today, likely due to changes in production practices, it has begun to re-emerge and again cause disease and death in hogs. 

SD is too costly a disease to live with. When an infection is suspected, it is important to get as early and accurate a diagnosis as possible. In many cases, if strong biosecurity measures are in place, the disease may be prevented from entering a farm in the first place.

History

SD was first described in 1921 in the Midwestern United States. By the early 1970s, the disease was prevalent in up to 38 percent of U.S. herds (1) and was estimated to cost the industry some $130 million annually. 

In 1971, the work of my research team at Iowa State University resulted in the discovery and naming of the cause of swine dysentery, Treponema hyodysenteriae, now called Brachyspira hyodysenteriae (2,3)At about the same time, and unknown to our team, researchers at Cambridge University made the same discovery, helping to validate our research (5).

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B. hyodysenteriae – photo: D.L. Harris

Due to this breakthrough discovery and subsequent research by many worldwide, swine dysentery became a disease of the past by the 1980s and had been mostly forgotten until its re-emergence at the turn of this century.

Recently, however, swine dysentery – also known as bloody scours – has been making resurgence. Typically affecting weaned/grower pigs, symptoms include severe diarrhea with blood and mucus.

HISTORY

SD was first described in 1921 in the Midwestern United States.  This devastating disease caused widespread disease and death loss in swine herds worldwide

In 1971, my research team at Iowa State University discovered and named the cause Treponema hyodysenteriae,

In the 1950s and 60s, swine dysentery caused economic havoc worldwide. In the U.S., the spread of the disease was exacerbated by the common movement of 30- to 50-pound feeder pigs into Iowa from small farrowing operations in the south. 

These farrowing operations were unknowingly infected with B. hyodysenteriae and apparently healthy feeder pigs were placed in finisher buildings, subsequently breaking with swine dysentery a few weeks after placement.

Pigs in farrow-to-feeder operations and even small purebred breeders were infected with B. hyodysenteriae but the disease went undetected because there is a good immunity in adult animals once recovered from the disease. 

Only when young pigs and young breeding animals were transported and co-mingled did the disease emerge with a vengeance, resulting in severe diarrhea containing blood and mucus with death rates reaching as high as 40 percent in some groups of pigs.

The discovery of B. hyodysenteriae set off a decade of intense research and epidemologic investigations. Individual herd disease eradication strategies were created and methods were developed for controlling swine dysentery without the need for depopulation. 

Based on serologic prevalence studies in the early 1970s, the incidence of the disease on Midwestern farms was as high as 38 percent. By the early 1980s, the disease appeared to be of little significance worldwide.  Numerous patents describing vaccines for prevention of swine dysentery have been granted – most are now expired – and a commercial vaccine was sold in the U.S. for a time but has since been removed from the market.

TODAY

I first became aware of the re-emergence of swine dysentery in 2004 when I was asked to investigate an outbreak in a large integrated operation in Spain.  I was in Germany attending the International Pig Veterinary Society meeting when contacted by the owners of the operation.  Of note, there were no presentations on swine dysentery at the 2004 IPVS meeting. 

Since 2004, reports of swine dysentery occurrence in the U.S. and Canada appear to have increased. 

In my opinion, two facts play heavily in the re-emergence of SD:

  1. Mice are a known reservoir for B. hyodysenteriae, which affects mice without causing disease so they can remain infected for more than a year; and
  2. Single-site farrow-to-isowean pigs operations appear to be uninfected due to B. hyodysenteriae immunity in the sow herd and colostral immunity in suckling pigs, making it difficult to detect infected farms. The large increase in movement of three-week-old isowean pigs from apparent subclinically affected farms has increased the occurrence of swine dysentery-positive isowean pigs entering wean-to-finish units in the Midwest. 

Other factors include difficulties in eradicating the B. hyodysenteriae from pits due to the difficulty in effectively cleaning and disinfecting all areas of the pit. Animals exposed to pit or lagoon water can be infected by the organisms still present.

In addition, research in Australia has indicated that dietary components can influence whether clinical signs of SD are easily recognizable (4).

The organism also survives in feces for 60 days at refrigerator temperature, so it can remain viable throughout the colder periods of the year.

Symptoms

SD effects pigs of all ages, but is most frequent in eight- to 14-week-old pigs. With a one- to three-week incubation period, SD infection results in sunken flanks and depression, diarrhea of loose to watery consistency with blood and mucus evident in the feces. 

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Pig exhibiting SD symptoms – photo: D.L. Harris

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Feces contain blood and mucus – photo: D.L. Harris

Microscopically, lesions are restricted to the large intestine, cecum, colon and rectum, edematous mesentery and intestinal wall. The colon contains mucus, fibrin and blood.

Diagnostic Tests

The most accurate determination of SD is to post pigs with clinical signs. A complete necropsy is recommended and tissues should be submitted to a diagnostic lab for accurate diagnosis.  Cultures of intestinal material from pigs with lesions of SD are both specific and sensitive for confirmation of the diagnosis.

Cultures of rectal swab samples are not a good way to diagnose SD. While they are very specific if the organism can be detected, they lack sensitivity. Using rectal swab material in the qPCR test can give misleading results due to a lack of both sensitivity and specificity.

Identification of SD infections

SD is often subclinically present in sow herds, providing maternal antibody immunity to baby pigs until they are weaned then the disease breaks when they are moved to grow-finish barns.

The best indicator of whether a sow farm is subclinically infected is whether Isowean pigs break with SD soon after placement in wean-finish barns.

In wean-finish barns, SD will occur if no drugs are present in feed or water to mask the disease.

Depopulation vs. elimination vs. living with SD

Based on costs in the 1980s, it was more economically feasible to eliminate the disease without depopulation rather than live with it or conduct a total depopulation (see table).  Currently, depopulation may be a viable option if additional diseases can be eradicated simultaneously. 

Financial Impact

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Polson, Marsh, Harris – 1992

Treatment options

Several drugs used in the 1980s for prevention, treatment, and elimination are no longer available.  Drugs currently approved for treatment and/or prevention can be found at http://www.accessdata.fda.gov/scripts/animaldrugsatfda/.  Research is ongoing to determine if any of these drugs can be used at approved levels for elimination without depopulation programs.  Consult a veterinarian for assistance in developing effective control programs

Control of swine dysentery in the future will depend on improved methods for detecting asymptomatically affected sow farms with the disease and the development of vaccines to prevent swine dysentery in growing pigs.

Immunity to SD

Research has shown that pigs which have recovered from SD without medication are immune to re-challenge, making vaccine therapy a viable option for controlling SD.

Further, pregnant gilts recovered from SD transmitted B. hyodysenteriae to their suckling pigs. These pigs did not show signs of SD while nursing, but became ill with the disease after weaning.

A commercial subunit vaccine previously approved by USDA has been removed from the market. An RNA Particle-based vaccine is now in development at Harrisvaccines and expected to be available soon.

Summary

The disease is difficult to diagnose definitively. If clinical signs and lesions are observed, intestinal tissue samples should be sent to a diagnostic lab for examination.

SD is too costly a disease to live with and biosecurity measures can prevent it from entering a farm in the first place. Though difficult, the disease can be eliminated via isowean pigs in multiple isolated site production practices.

Reference List

 

   1.   Egan, I. T., D. L. Harris, and H. T. Hill. 1982. Prevalence of Swine Dysentery, Transmissible Gastroenteritis, and Pseudorabies in Iowa, Illinois and Missouri Swine. Proceedings 86th U. S. Annual Health Assoc. Meeting 497-502.

   2.   Glock, R. D. and D. L. Harris. 1972. Swine dysentery – II. Veterinary Medicine/Small Animal Clinician 67:65-68.

   3.   Harris, D. L., R. D. Glock, C. R. Christensen, and J. M. Kinyon. 1972. Swine Dysentery – I Inoculation of Pigs with Treponema hyodysenteriae (new species) and Reproduction of the Disease. Veterinary Medicine/Small Animal Clinician 67:61-64.

   4.   Pluske, J. R., P. M. Siba, D. W. Pethick, Z. Durmic, B. P. Mullan, and D. J. Hampson. 1996. The Incidence of Swine Dysentery in Pigs Can Be Reduced by Feeding Diets That Limit the Amount of Fermentable Substrate Entering the Large Intestine. American institute of Nutrition 126:2920-2933.

   5.   Taylor, D. J. and T. J. L. Alexander. 1971. The Production of Dysentery in Swine by Feeding Cultures Containing a Spirochaete. Br. vet. J. 127:lviii-lxi.